Amelioration of D-galactosamine-induced acute liver injury in rats by dietary supplementation with betaine derived from sugar beet molasses

The effects of betaine supplementation on D-galactosamine-induced liver injury were examined in terms of hepatic and serum enzyme activities and of the levels of glutathione and betaine-derived intermediates. The rats induced with liver injury showed marked increases in serum enzyme activity, but those receiving dietary supplementation of 1% betaine showed enzyme activity levels similar to a control group without liver injury. Administration of betaine also increased both hepatic and serum glutathione levels, even following D-galactosamine injection. The activity of glutathione-related enzymes was markedly decreased following injection of D-galactosamine, but remained comparable to that of the control group in rats receiving 1% betaine. The concentrations of hepatic S-adenosyl methionine and cysteine showed similar trends to that observed for hepatic glutathione levels. These results indicate that 1% betaine has a hepatoprotective effect by increasing hepatic and serum glutathione levels along with glutathione-related enzyme activities in rats.     

Suppression of D-galactosamine-induced rat liver injury by glycosidic flavonoids-rich fraction from green tea

Tea constituents that had a preventive effect on D-galactosamine-induced liver injury in rats were partially purified by column chromatography from a n-butanol-soluble fraction of green tea. The fraction containing glycosidic flavonoids was found to suppress the D-galactosamine-induced increase of plasma alanine aminotransferase and aspartate aminotransferase activities. These results indicate that glycosidic flavonoids contribute, at least in part, to the liver injury-preventive effect of green tea.     

Glycosidic flavonoids as rat-liver injury preventing compounds from green tea

A glycosidic flavonoids-rich fraction from green tea leaves was purified to isolate five glycosidic flavonoids, guided by the detection of a preventive effect on D-galactosamine-induced liver injury in rats. These were identified as a flavone C-glycoside (1) and trisaccharide flavonols (2-5) based on the spectroscopic analyses. These compounds suppressed the D-galactosamine-induced increase of plasma alanine aminotransferase and asparatate aminotransferase activities in rats.     

STAT1 plays an essential role in LPS/D-galactosamine-induced liver apoptosis and injury

Interferon-gamma (IFN-gamma) has been implicated in liver damage in animal models and chronic hepatitis C infection; however, the underlying mechanism is not clear. Here we examined the role of STAT1, a key signaling molecule for IFN-gamma, in a model of murine hepatitis induced by the injection of LPS/D-galactosamine and in human hepatoma Hep3B cells. STAT1 is rapidly activated and highly induced after injection of LPS/D-galactosamine. Both overexpression of STAT1 and hepatocellular damage are located in the same pericentral region. Disruption of the STAT1 gene abolishes LPS/D-galactosamine-induced liver injury. Studies from IFN-gamma-deficient mice indicate that IFN-gamma is the major cytokine responsible for activation and hyperexpression of STAT1 in LPS/D-galactosamine-induced hepatitis. Hep3B cells overexpressing dominant negative STAT1 are resistant to IFN-gamma and IFN-gamma + TNF-alpha-induced cell death, whereas Hep3B cells overexpressing wild-type STAT1 are more susceptible to cell death. Taken together, these findings suggest that STAT1 plays an essential role in LPS/D-galactosamine-induced liver apoptosis and injury.     

Effects of dietary protein of proso millet on liver injury induced by D-galactosamine in rats

In this paper, we examined the effects of dietary protein from proso millet on liver injury induced by D-galactosamine or carbon tetrachloride in rats using serum enzyme activities as indices. D-galactosamine-induced elevations of serum activities of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase were significantly suppressed by feeding the diet containing 20% protein of proso millet for 14 days as compared with those of rats fed a 20% casein diet, but not in the case of carbon tetrachloride. The results showed that proso millet protein is effective at lower dietary protein levels than that of dietary gluten reported previously. Therefore, the findings reported here may suggest that proso millet protein is considered to be another preventive food for liver injury.     

Suppression of D-galactosamine-induced liver injury by mushrooms in rats

Six species of edible mushroom were found to suppress D-galactosamine-induced enhancement of plasma alanine and aspartate aminotransferase activities when powdered mushrooms were added to the diet (5%) and fed to rats for 2 wk. Grifola frondosa exhibited the most potent effect in a dose-dependent manner. A significant effect was observed only from the water-soluble low-molecular-weight fraction of G. frondosa. The results indicate that several mushrooms possess a protective effect against liver injury induced by D-galactosamine.     

In Vitro Peptidoglycan Synthesis Which is Very Sensitive to Cephalexin and Penicillin G in Escherichia coli: Presumable Septum-forming Reaction Sequence

Hydrangeae Dulcis Folium, the fermented and dried leaves of Hydrangea macrophylla SER. var. thunbergii MAKINO, suppressed D-galactosamine-induced liver injury by 85.2% when added to the diet at 1% and fed to rats for fifteen days. The hepatoprotective effect is more potent than that of a milk thistle extract and turmeric powder. Some fractionated extracts showed hepatoprotective activity in the D-galactosamine-induced in vitro liver injury model.     

Rare earth cerium oxide nanoparticles attenuated liver fibrosis in bile duct ligation mice model

Liver fibrosis is one of the major liver complications which eventually progresses to liver cirrhosis and liver failure. Cerium oxide nanoparticles, also known as nanoceria (NC) are nanoparticles with potential antioxidant and anti-inflammatory activities. Herein, we evaluated the hepatoprotective and anti-fibrotic effects of nanoceria (NC) against bile duct ligation (BDL) induced liver injury. NC were administered i.p. for 12 days (0.5 and 2 mg/kg) to C57BL/6J mice. The biochemical markers of liver injury, oxidative and nitrosative stress markers, inflammatory cytokines were evaluated. Fibrosis assessment and mechanistic studies were conducted to assess the hepatoprotective effects of NC. Administration of NC proved to significantly ameliorate liver injury as evident by reduction in SGOT, SGPT, ALP and bilirubin levels in the treated animals. NC treatment significantly reduced the hydroxyproline levels and expression of fibrotic markers. In summary, our findings establish the hepatoprotective and anti-fibrotic effects of NC against BDL induced liver injury and liver fibrosis. These protective effects were majorly ascribed to their potential ROS inhibition and antioxidant activities through catalase, superoxide dismutase (SOD)-mimetic properties and auto-regenerating capabilities.     

Liver protection by bis(maltolato)zinc(II) complex.

The aim of this study was to perform screening of a novel drug for treating liver injury. Bis(maltolato)zinc(II) complex [Zn(Mal)(2)], which was previously reported to possess insulinomimetic activity, was found to have potency against experimentally induced liver injury both in vitro and in vivo. Cultured rat hepatocytes were treated with bromobenzene for 24 h to induce cellular injury. Zn(Mal)(2) of various concentrations was added along with bromobenzene in order to evaluate the hepatoprotective activity of Zn(Mal)(2) in vitro. The number of viable hepatocytes decreased by 42% in the culture with bromobenzene. However, hepatocyte viability was maintained when Zn(Mal)(2) was added to the bromobenzene culture. The hepatoprotective activity of Zn(Mal)(2) in vivo was investigated using a concanavalin A-induced liver injury model in BALB/c mice. Changes in serum aminotransferase activities and the secretion of several cytokines were measured. The hepatoprotective effect of Zn(Mal)(2) was also demonstrated in vivo by the suppression of serum aspartate aminotransferase and alanine aminotransferase elevation. No significant changes in serum cytokines associated with the induction of hepatic damage were observed in the concanavalin A-induced injury model. However, examination of concanavalin A-treated mouse splenocytes revealed a dose-dependent suppression of cytokine secretions by Zn(Mal)(2). Zn(Mal)(2) possessed hepatoprotective activity and might exert its effect by a number of mechanisms.     

Anastatins A and B,new skeletal flavonoids with hepatoprotective activities from the desert plant Anastatica hierochuntica

New skeletal flavonoids, anastatins A and B, were isolated from the methanolic extract of an Egyptian medicinal herb, the whole plants of Anastatica hierochuntica. Their flavanone structures having a benzofuran moiety were determined on the basis of chemical and physicochemical evidence. Anastatins A and B were found to show hepatoprotective effects on D-galactosamine-induced cytotoxicity in primary cultured mouse hepatocytes and their activities were stronger than those of related flavonoids and commercial silybin.     

Oral Hepatoprotective Ability Evaluation of Purple Sweet Potato Anthocyanins on Acute and Chronic Chemical Liver Injuries

In recent years, chemical liver injury cases increased significantly in Asian countries, and the imbalance in redox system was believed to be the main cause. Purple sweet potato anthocyanins (PSPA) have been shown to exert antioxidant activity and oxidative-stress-associated functional protein modulation through various signaling pathways, so it is considered to have the potential of liver injury preventive activity. In order to evaluate the hepatoprotective potency of PSPA according to its free radical scavenging and antioxidant effects, three acute chemical liver injury models were set up with ethanol, acetaminophen and carbon tetrachloride. PSPA at moderate and high doses obviously attenuated the tested serum biomarker levels and liver index in our experiments. Besides, one chronic liver injury model set up with carbon tetrachloride was also applied, in which PSPA was orally administrated after the liver damage had been formed. Both the serum biomarker levels and histopathological analysis showed that PSPA was able to attenuated chronic liver injury. Our experimental results demonstrated the potential of PSPA as an oral hepatoprotective agent against chemical liver injury from food plant.     

灵芝总三萜对鹅膏毒肽中毒小鼠所致肝损伤的保护作用研究

鹅膏肽类毒素是蘑菇中毒导致死亡的最主要因素,用于鹅膏中毒治疗的解毒药物已有大量报道,水飞蓟宾（silibinin,SIL）被认为是目前最有效的解毒药物。灵芝作为我国传统的中药真菌,具有良好的保肝护肝作用。本文开展灵芝主要活性成分灵芝总三萜（Ganoderma total triterpenoids,GTT）和对照药物水飞蓟宾对α-鹅膏毒肽（α-amanitin,α-AMA）中毒小鼠所致肝损伤的保护作用及其抗氧化机理研究,结果表明α-鹅膏毒肽中毒小鼠经灵芝总三萜和水飞蓟宾治疗后小鼠血清中的ALT和AST活性显著降低,小鼠死亡率降低40%-50%,病理组织切片观察表明能明显减轻肝组织损伤的程度,说明灵芝总三萜与水飞蓟宾一样,对α-鹅膏毒肽中毒小鼠的肝具有很好的保护作用。灵芝总三萜给药组和水飞蓟宾给药组能显著增加肝组织中SOD和CAT的活性,显著降低肝脏中MDA含量,表明灵芝总三萜和水飞蓟宾具有抗氧化和自由基清除剂作用,能减轻α-鹅膏毒肽所引起的脂质过氧化伤害作用。     

具有保肝作用的天然药物开发进展

肝脏是机体代谢的最主要场所,也是机体最容易遭受到损伤的脏器之一,各种因素引起的肝损伤已成为威胁人类健康的重要疾病之一。肝损伤机制主要与线粒体损伤、自由基脂质过氧化、炎症细胞因子分泌和细胞膜损伤有关。目前已报道很多天然药物具有显著保肝作用,且具有疗效稳定、副作用低、多途径作用、作用温和持久等优势,已广泛用于肝脏疾病的防治。本文对肝损伤的生理机制以及具有保肝作用的天然药物开发进展进行了综述,提出了目前存在的一些问题并进行了展望。     

Hepatoprotective effect of pyrroloquinoline quinone against alcoholic liver injury through activating Nrf2-mediated antioxidant and inhibiting TLR4-mediated inflammation responses

The present study was aimed at investigating the hepatoprotective effect of pyrroloquinoline quinone (PQQ) against acute alcoholic liver injury in mice. Acute alcoholic liver injury model was established in mice, and they were administrated with PQQ to investigate its hepatoprotective effect. Our results shows that PQQ can significantly ameliorate acute alcoholic liver injury by decreasing the hepatic marker enzymes, including serum alanine transaminase (ALT) and aspartate transaminase (AST), and increasing the levels of alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in the liver. And PQQ can also significantly reduce the content of hepatic triglyceride (TG) and malondialdehyde (MDA). Moreover, PQQ attenuated alcohol-induced oxidative damage by activating NF-E2-related factor 2 (Nrf2)-mediated signaling pathway, and inhibiting Toll-like receptor 4 (TLR4)-mediated nuclear factor-kappa B (NF-κB) signaling pathway. Our findings have elucidated the liver protection mechanism of PQQ, which would encourage the further exploitation of PQQ as a hepatoprotective functional food.     

New hepatoprotective coumarinolignoids from Mallotus apelta

Three new coumarinolignoids, malloapelins A-C (1-3, resp.), together with three known coumarinolignoids, cleomiscosin A (4), cleomiscosin B (5), and 5'-demethylaquillochin (6), were isolated from the roots of Mallotus apelta MUELL.-ARG. Compounds 1-6 are three pairs of regioisomeric coumarinolignoids. Their structures were elucidated on the basis of spectral evidence. Compounds 3 showed promising hepatoprotective activity against D-galactosamine-induced toxicity in WB-F344 rat hepatic epithelial stem-like cells.     

Suppression of lipopolysaccharide-induced liver injury by various types of tea and coffee in D-galactosamine-sensitized rats

Extracts of various types of tea and coffee significantly suppressed lipopolysaccharide (LPS)-induced liver injury, as assessed by the plasma enzyme activities, in D-galactosamine-sensitized rats when administered orally once before injecting the drugs. There was a significant negative correlation between the caffeine levels of these extracts and liver injury. Authentic caffeine also had a hepatoprotective effect. These results suggest that caffeine-containing beverages generally suppress LPS-induced liver injury according to their caffeine content.     

Hepatoprotective activity of Psidium guajava Linn. leaf extract

The study was designed to evaluate the hepatoprotective activity of P. guajava in acute experimental liver injury induced by carbon tetrachloride, paracetamol or thioacetamide and chronic liver damage induced by carbon tetrachloride. The effects observed were compared with a known hepatoprotective agent, silymarin. In the acute liver damage induced by different hepatotoxins, P. guajava leaf extracts (250 and 500mg/kg, po) significantly reduced the elevated serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and bilirubin. The higher dose of the extract (500 mg/kg, po) prevented the increase in liver weight when compared to hepatoxin treated control, while the lower dose was ineffective except in the paracetamol induced liver damage. In the chronic liver injury induced by carbon tetrachloride, the higher dose (500 mg/kg, po) of P. guajava leaf extract was found to be more effective than the lower dose (250 mg/kg, po). Histological examination of the liver tissues supported the hepatoprotection. It is concluded that the aqueous extract of leaves of guava plant possesses good hepatoprotective activity.     

Hydroxysafflor yellows alleviate thrombosis and acetaminophen-induced toxicity in vivo by enhancing blood circulation and poison excretion

BackgroundHydroxysafflor yellow A (HSYA) from the flower of Carthamus tinctorius (Safflower) has been reported to have various pharmacological effects. However, little is known about the bioactivities of other chemical constituents in Safflower and the relationship between enhancement of blood circulation and hepatoprotection by HSYA.PurposeThe present research was to evaluate the antithrombotic and hepatoprotective activities of HSYA and C, examine their mechanisms of actions, including influence on the excretion velocity of acetaminophen, and the relationship between the antithrombotic, hepatoprotective, and other bioactivities.MethodsThe hepatoprotective activities were examined by acetaminophen (APAP)-induced zebrafish toxicity and carbon tetrachloride (CCl₄)-induced mouse liver injury. The concentrations of APAP in zebrafish and APAP that was excreted to the culture media were quantified by UHPLC-MS. The anti-thrombosis effect of HSYA and C were examined by the phenylhydrazine (PHZ)-induced zebrafish thrombosis.ResultsHSYA and HSYC showed robust protection on APAP-induced toxicity and PHZ-induced thrombosis. The hepatoprotective effects of HSYA and C were more potent than that of the positive control, acetylcysteine (61.7% and 58.0%, respectively, vs. 56.9% at 100 µM) and their antithrombosis effects were more robust than aspirin (95.1% and 86.2% vs. 52.7% at 100 µM). HSYA and C enhanced blood circulation, rescued APAP-treated zebrafish from morphological abnormalities, and mitigated APAP-induced toxicity in liver development in liver-specific RFP-expressing transgenic zebrafish. HSYC attenuated CCl₄-induced mouse liver injury and regulated the levels of HIF-1α, iNOS, TNF-α, α-SMA, and NFκB in liver tissues. HSYA was also protective in a dual thrombotic and liver toxicity zebrafish model. By UHPLC-MS, HSYA accelerated the excretion of APAP.ConclusionHSYA and C are the bioactive constituents of Safflower that are responsible for the herbal drug's traditional use in promoting blood circulation to remove blood stasis. Safflower and its chalcone constituents may protect from damage due to exogenous or disease-induced endogenous toxins by enhancing the excretion velocity of toxins.     

Hepatoprotective constituents from zedoariae rhizoma: absolute stereostructures of three new carabrane-type sesquiterpenes, curcumenolactones A, B, and C

New carabrane-type sesquiterpene lactones, curcumenolactones A, B, and C, were isolated from the 80% aqueous acetone extract of Zedoariae Rhizoma (Zingiberaceae), together with 41 sesquiterpenes and two diarylheptanoids. The absolute stereostructures of curcumenolactones A, B, and C were determined on the basis of physicochemical evidence, which included nuclear Overhauser effect (NOE) and circular dichroic (CD) spectroscopic analyses. Curcumenone, a principal carabrane-type sesquiterpene from Zedoariae Rhizoma, was found to show potent protective effect on D-galactosamine/lipopolysaccharide-induced acute liver injury in mice. In addition, curcumenolactones A and B and the other constituents showed protective effect on D-galactosamine-induced cytotoxicity in primary cultured rat hepatocytes.